Nadine M. Tung, MD
Director, Cancer Risk and Prevention Program
Beth Israel Deaconess Medical Center
Associate Professor of Medicine, Harvard Medical School
Beth Israel Deaconess Medical Center
Determining predictors of chemotherapy response in BRCA-driven breast cancers.
The BRCA1 and BRCA2 genes are the most commonly mutated genes in hereditary breast and ovarian cancers. Normally, BRCA 1 and BRCA2 function to ensure the proper repair of DNA damage, but mutations in these genes lead to rapid accumulation of DNA errors, which is the underlying cause of cancer. However, this defect also makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Drs. Tung and Schnitt are working to understand the unique characteristics of breast tumors from patients with inherited BRCA1 or BRCA2 mutations to identify predictors of response and resistance to chemotherapy and ultimately improve treatment strategies for BRCA-driven breast and ovarian cancers.
Drs. Tung and Schnitt are identifying features of breast tumors that predict response to chemotherapy in BRCA-driven breast cancers. The team completed the INFORM trial, which demonstrated that cisplatin is an active chemotherapy in BRCA mutation carriers with breast cancer. While they did not find it to be more effective than the standard chemotherapy regimen, it provides another treatment option for patients. Drs. Tung and Schnitt are analyzing blood and tumor specimens collected from INFORM participants to better understand the molecular landscape of these cancers and to discover biomarkers of response to cisplatin and standard chemotherapy. So far, they found through genomic analysis that 89 percent of breast cancers in BRCA carriers have lost one copy of the gene and its surrounding region on the chromosome. They have also found some tumors that each have hundreds of chromosomal rearrangements in one or several regions, which are highly associated with resistance to chemotherapy.
In the upcoming year, Drs. Tung and Schnitt will continue performing genomic analyses to probe more deeply into chromosomal rearrangements, evaluating on which chromosomes they occur, where on the chromosome they occur, and patterns of rearrangement. They will also continue analysis of INFORM biospecimens to determine genetic predictors of chemotherapy response and to identify mutations that could affect the efficacy of PARP inhibitors, which are commonly used to treat BRCA-driven breast cancers. Finally, Drs. Tung and Schnitt will continue to work on an artificial intelligence model for response to chemotherapy. Towards this end, they plan to explore whether any clinical variables (tumor stage, patient age, etc.) increase the accuracy of the model generated from pathology features, then test the model on data from an independent cohort of patients from another clinical trial.
Nadine Tung, MD is the Director of the Cancer Genetics and Prevention Program at Beth Israel Deaconess Medical Center (BIDMC) which she established in 1997 to evaluate patients and families with hereditary cancer syndromes. She is also a breast medical oncologist and a member of the Dana-Farber Harvard Cancer Center as well as an Associate Professor at Harvard Medical School. She graduated from Princeton University in 1980 and Harvard Medical School in 1984.
Dr. Tung's research focuses on hereditary causes of breast cancer as well as effective strategies for breast cancer prevention and treatment. Much of her research has focused on women with BRCA1 and BRCA2 mutations, studying the genetic and environmental factors that influence cancer development as well as the biology and prognosis of the breast cancers they develop. Through BCRF, she is overseeing a multi-center, national trial evaluating whether cisplatin is superior to standard chemotherapy for women with BRCA1/2 mutations and newly diagnosed breast cancer. Her research also focuses on identifying other inherited gene mutations that predispose to breast cancer. Other areas of Dr. Tung’s research include evaluating the prognosis and optimal treatment of triple- negative breast cancer. Dr. Tung serves on the Editorial Board of the Journal of Clinical Oncology as well as the American Society of Clinical Oncology’s Cancer Prevention Committee and Cancer Genetics Subcommittee.
The Joan Lunden Award
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